The clinical trial protocols of this renewal application have been designed to improve the state-of-the-art in clinical islet transplantation. CIT-04/06/07 Trials: The CIT-04 trial is a prospective, two-center (Edmonton and Emory), open-label, pilot study of islet transplantation assessing the safety and efficacy of a steroid-free, calcineurin inhibitor-free belatacept based immunosuppressive medication in subjects with long-standing T1D that is refractory to intensive insulin therapy. We believe the CIT-04 study is a unique opportunity to bring co-stimulation blockade to the forefront of clinical islet transplant practice. The two centers participating in this phase 2 study will also undertake a separate, phase 3 study in islet transplantation, using a standard manufacturing and immunosuppressive regimen. The phase 3 trial. Protocol CIT-07, will have inclusion/exclusion criteria and endpoint measures that are identical to those in this phase 2 trial. In order to avoid bias in selection of subjects, eligible subjects will be randomized, prior to transplantation, to participate either in this phase 2 or the multi-center phase 3 study. The CIT-06 study will be a prospective, single-arm, multi-center clinical trial in kidney transplant recipients with T1D, assessing the effect of islet transplantation. The research plan is to enroll a total of 20 subjects in CIT-04 to receive Belatacept with both Edmonton and Emory contributing patients to this trial. It is proposed that Edmonton will enroll 12 subjects in CIT-04 and Emory 8 subjects, for a total of 20. It is also anticipated that Edmonton will enroll 6 subjects in CIT-07 (the comparison transplant group without Belatacept) with 2 to 1 randomization at the Edmonton site towards the Belatacept arm. It is expected that Emory will enroll 8 subjects in CIT-07 to match the 1 to 1 randomization between CIT-04 and CIT-07 at the Emory site. We will both contribute subjects to CIT-06 (islet after kidney transplantation, with at least 4 subjects per site). As part of the CIT consortium, Edmonton's continued participation in these three trials will help refine future islet transplantation therapy. RELEVANCE (taken from the application): The clinical protocols developed by the CIT consortium have been designed to significantly improve the current state-of-the-art in clinical islet transplantation. Specifically: CIT-07 has been designed to include current accepted standard practice in pre, peri and post islet transplantation. Results from CIT-07 will be used to obtain FDA biological licensure. CIT-04 will study a novel co-stimulation blockade (Belatacept)/CellCept immunosuppressant regime to improve safety/tolerability of maintenance therapy. CIT-06 will investigate the efficacy of CIT in kidney transplant patients. The overall goal of the CIT-04/06/07 trials is to improve insulin independence duration of islet transplant patients, most preferred with islets from single donor organs. The combination of the CIT consortium trials will change the face of future clinical islet transplantation therapy.